ERCC4 (xeroderma pigmentosum, complementation group F)

ERCC4 (xeroderma pigmentosum, complementation group F)

2001-05-01 Anne Stary , Alain Sarasin Affiliation

Laboratory of Genetic Instability, Cancer, UPR2169 CNRS, Institut de Recherches sur le Cancer, 7, rue guy Moquet, BP 8, 94801 VILLEJUIF, France

Identity

HGNC

LOCATION

16p13.12

IMAGE

Atlas Image

LEGEND

XPF (16p13) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.

LOCUSID

ALIAS

ERCC11,FANCQ,RAD1,XFEPS,XPF

FUSION GENES

Show Gene Fusions

DNA/RNA

Description

28.2 kb

Transcription

2881 bp =D0 11 exons

Proteins

Description

xeroderma pigmentosum group F complementing factor; DNA-repair protein complementing XPF cells 905 amino acids; form a stable complex with the ERCC1 protein; The XPF protein and the ERCC1 protein form a complex that exhibits structure specific endonuclease activity that is responsible for the 5 incision during the NER reaction. XPF-ERCC1 also binds to XPA (through ERCC1) and to RPA (through XPF) but not preferentially to damaged DNA. At the site of a lesion Nucleotide Excision Repair (NER) proteins create a DNA bubble structure over a length of approximately 25 nucleotides and the XPG protein incises the damaged DNA strand 0-2 nucleotides 3 to the ssDNA-dsDNA junction. In most studies the 3-incision made by the XPG protein appeared to be made prior to and independently of the 5-incision by XPF-ERCC1. XP-F patients have a relatively mild XP phenotype without neurological abnormalities. Cells from XP-F patients are slightly UV-sensitive and exhibit low levels of repair initially after UV-irradiation.

The XPF protein is a single-stranded DNA endonuclease that is also involved in a pathway of recombination repair of DNA interstrand crosslinks.

Homology

Substantial homology with the eucaryotic DNA repair and recombination proteins MEI-9 (Drosophila melanogaster), Rad16 (Saccharomyces cerevisae) and Rad1 (Schizosaccharomyces pombe).

Mutations

Germinal

9 point mutations ; 3 small deletions ; 1 small insertion ; 1 gross deletion

Implicated in

Entity name

xeroderma pigmentosum, XP group F

Disease

Early skin tumours in XPF patients

Bibliography

Pubmed ID	Last Year	Title	Authors
7697716	1995	Mammalian DNA nucleotide excision repair reconstituted with purified protein components.	Aboussekhra A et al
10673506	2000	Nucleotide excision repair of DNA with recombinant human proteins: definition of the minimal set of factors, active forms of TFIIH, and modulation by CAK.	Araújo SJ et al
9013642	1997	Reconstitution of human excision nuclease with recombinant XPF-ERCC1 complex.	Bessho T et al
8253090	1993	Co-correction of the ERCC1, ERCC4 and xeroderma pigmentosum group F DNA repair defects in vitro.	Biggerstaff M et al
9447231	1997	Excision-repair patch lengths are similar for transcription-coupled repair and global genome repair in UV-irradiated human cells.	Bowman KK et al
8887684	1996	ERCC4 (XPF) encodes a human nucleotide excision repair protein with eukaryotic recombination homologs.	Brookman KW et al
11285194	2001	Genetic polymorphisms in DNA repair genes and risk of lung cancer.	Butkiewicz D et al
9351836	1997	Mechanism of open complex and dual incision formation by human nucleotide excision repair factors.	Evans E et al
11160918	2001	Activity of individual ERCC1 and XPF subunits in DNA nucleotide excision repair.	Gaillard PHL et al
9653453	1998	ERCC1 mutations in UV-sensitive Chinese hamster ovary (CHO) cell lines.	Hayashi T et al
10320375	1999	Action of DNA repair endonuclease ERCC1/XPF in living cells.	Houtsmuller AB et al
2664729	1989	Late onset of skin cancers in 2 xeroderma pigmentosum group F siblings and a review of 30 Japanese xeroderma pigmentosum patients in groups D, E and F.	Kondo S et al
8332082	1993	Regional mapping of human DNA excision repair gene ERCC4 to chromosome 16p13.13-p13.2.	Liu P et al
9580660	1998	Characterization of molecular defects in xeroderma pigmentosum group F in relation to its clinically mild symptoms.	Matsumura Y et al
8626644	1996	Replication protein A confers structure-specific endonuclease activities to the XPF-ERCC1 and XPG subunits of human DNA repair excision nuclease.	Matsunaga T et al
10413517	1999	Domain mapping of the DNA binding, endonuclease, and ERCC1 binding properties of the human DNA repair protein XPF.	McCutchen-Maloney SL et al
8427828	1993	A case of xeroderma pigmentosum complementation group F with neurological abnormalities.	Moriwaki S et al
8626523	1996	Reaction mechanism of human DNA repair excision nuclease.	Mu D et al
8613681	1996	ERCC1/ERCC4 5'-endonuclease activity as a determinant of hypoxic cell radiosensitivity.	Murray D et al
1814424	1991	Xeroderma pigmentosum patients belonging to complementation group F and efficient liquid-holding recovery of ultraviolet damage.	Nishigori C et al
10669734	2000	Terminally differentiated human neurons repair transcribed genes but display attenuated global DNA repair and modulation of repair gene expression.	Nouspikel T et al
7559382	1995	Purification and characterization of the XPF-ERCC1 complex of human DNA repair excision nuclease.	Park CH et al
8197175	1994	Formation of a ternary complex by human XPA, ERCC1, and ERCC4(XPF) excision repair proteins.	Park CH et al
2929593	1989	Human chromosome 15 confers partial complementation of phenotypes to xeroderma pigmentosum group F cells.	Saxon PJ et al
9579555	1998	Homozygous R788W point mutation in the XPF gene of a patient with xeroderma pigmentosum and late-onset neurologic disease.	Sijbers AM et al
8041709	1994	Molecular cloning of the human nucleotide-excision-repair gene ERCC4.	Thompson LH et al
9188507	1997	The non-catalytic function of XPG protein during dual incision in human nucleotide excision repair.	Wakasugi M et al
9197240	1997	Disruption of mouse ERCC1 results in a novel repair syndrome with growth failure, nuclear abnormalities and senescence.	Weeda G et al
11141066	2001	Novel functional interactions between nucleotide excision DNA repair proteins influencing the enzymatic activities of TFIIH, XPG, and ERCC1-XPF.	Winkler GS et al
10214908	1999	DNA damage recognition during nucleotide excision repair in mammalian cells.	Wood RD et al
9862190	1998	Sensitivity of group F xeroderma pigmentosum cells to UV and mitomycin C relative to levels of XPF and ERCC1 overexpression.	Yagi T et al
9472693	1998	Complete restoration of normal DNA repair characteristics in group F xeroderma pigmentosum cells by over-expression of transfected XPF cDNA.	Yagi T et al
2039995	1991	Analysis of point mutations in an ultraviolet-irradiated shuttle vector plasmid propagated in cells from Japanese xeroderma pigmentosum patients in complementation groups A and F.	Yagi T et al
9025096	1997	A low content of ERCC1 and a 120 kDa protein is a frequent feature of group F xeroderma pigmentosum fibroblast cells.	Yagi T et al
6321052	1984	Xeroderma pigmentosum fibroblasts are more sensitive to asbestos fibers than are normal human fibroblasts.	Yang LL et al
9525876	1998	DNA structural elements required for ERCC1-XPF endonuclease activity.	de Laat WL et al
7596355	1995	Partial characterization of the DNA repair protein complex, containing the ERCC1, ERCC4, ERCC11 and XPF correcting activities.	van Vuuren AJ et al

Other Information

Locus ID:

NCBI: 2072
MIM: 133520
HGNC: 3436
Ensembl: ENSG00000175595

Variants:

dbSNP: 2072
ClinVar: 2072
TCGA: ENSG00000175595
COSMIC: ERCC4

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000175595	ENST00000311895	Q92889
ENSG00000175595	ENST00000311895	A0A1W1GSK9
ENSG00000175595	ENST00000462862	I3L4K0
ENSG00000175595	ENST00000574194	I3NI48
ENSG00000175595	ENST00000575156	Q92889
ENSG00000175595	ENST00000575156	A0A1W1GSP5

Expression (GTEx)

0

5

10

15

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Nucleotide excision repair	KEGG	ko03420
Nucleotide excision repair	KEGG	hsa03420
Fanconi anemia pathway	KEGG	ko03460
Fanconi anemia pathway	KEGG	hsa03460
DNA Repair	REACTOME	R-HSA-73894
DNA Double-Strand Break Repair	REACTOME	R-HSA-5693532
Homology Directed Repair	REACTOME	R-HSA-5693538
HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA)	REACTOME	R-HSA-5693567
HDR through Single Strand Annealing (SSA)	REACTOME	R-HSA-5685938
Nucleotide Excision Repair	REACTOME	R-HSA-5696398
Global Genome Nucleotide Excision Repair (GG-NER)	REACTOME	R-HSA-5696399
Formation of Incision Complex in GG-NER	REACTOME	R-HSA-5696395
Dual Incision in GG-NER	REACTOME	R-HSA-5696400
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	REACTOME	R-HSA-6781827
Dual incision in TC-NER	REACTOME	R-HSA-6782135
Fanconi Anemia Pathway	REACTOME	R-HSA-6783310

Protein levels (Protein atlas)

Not detected

Low

Medium

High

PharmGKB

Entity ID	Name	Type	Evidence	Association	PK	PD	PMIDs
PA164713176	Platinum compounds	Chemical	ClinicalAnnotation	associated		PD	25069034
PA443622	Carcinoma, Non-Small-Cell Lung	Disease	ClinicalAnnotation	associated		PD	25069034

References

Pubmed ID	Year	Title	Citations
36070459	2023	Association of ERCC1 and XPF polymorphisms with pediatric glioma susceptibility.	1
36070459	2023	Association of ERCC1 and XPF polymorphisms with pediatric glioma susceptibility.	1
34633654	2022	F-circEA1 regulates cell proliferation and apoptosis through ALK downstream signaling pathway in non-small cell lung cancer.	4
34837148	2022	The link of ERCC2 rs13181 and ERCC4 rs2276466 polymorphisms with breast cancer in the Bangladeshi population.	5
35780063	2022	Association of nonsynonymous SNPs of nucleotide excision repair genes ERCC4 rs1800067 (G/A) and ERCC5 rs17655 (G/C) as predisposing risk factors for gallbladder cancer.	0
34633654	2022	F-circEA1 regulates cell proliferation and apoptosis through ALK downstream signaling pathway in non-small cell lung cancer.	4
34837148	2022	The link of ERCC2 rs13181 and ERCC4 rs2276466 polymorphisms with breast cancer in the Bangladeshi population.	5
35780063	2022	Association of nonsynonymous SNPs of nucleotide excision repair genes ERCC4 rs1800067 (G/A) and ERCC5 rs17655 (G/C) as predisposing risk factors for gallbladder cancer.	0
33202356	2021	DNA base excision repair and nucleotide excision repair proteins in malignant salivary gland tumors.	4
33347546	2021	SLX4-XPF mediates DNA damage responses to replication stress induced by DNA-protein interactions.	8
33827099	2021	Contribution of XPD and XPF Polymorphisms to Susceptibility of Non-Small Cell Lung Cancer in High-Altitude Areas.	0
33931939	2021	The ZEB2-dependent EMT transcriptional programme drives therapy resistance by activating nucleotide excision repair genes ERCC1 and ERCC4 in colorectal cancer.	13
34416547	2021	XPF -673C>T variation is associated with the susceptibility to breast cancer.	0
33202356	2021	DNA base excision repair and nucleotide excision repair proteins in malignant salivary gland tumors.	4
33347546	2021	SLX4-XPF mediates DNA damage responses to replication stress induced by DNA-protein interactions.	8

Citation

Anne Stary ; Alain Sarasin

ERCC4 (xeroderma pigmentosum, complementation group F)

Atlas Genet Cytogenet Oncol Haematol. 2001-05-01

Online version: http://atlasgeneticsoncology.org/gene/299/case-report-explorer/meetings/js/lib/bootstrap.min.js